| Project/Area Number |
05670496
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| Research Category |
Grant-in-Aid for General Scientific Research (C)
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| Allocation Type | Single-year Grants |
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| Research Field |
Gastroenterology
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| Research Institution | Showa University |
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Principal Investigator |
YOSHIBA Makoto Showa university Department of Medicine associate professor, 医学部, 助教授 (20010457)
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| Co-Investigator(Kenkyū-buntansha) |
INOUE Kazuaki Showa university Department of Medicine Instructor, 医学部, 助手 (90232529)
SEKIYAMA Kazuhiko Showa university Department of Medicine Instructor, 医学部, 助手 (90211391)
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| Project Period (FY) |
1993 – 1994
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| Project Status |
Completed (Fiscal Year 1994)
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| Budget Amount *help |
¥2,100,000 (Direct Cost: ¥2,100,000)
Fiscal Year 1994: ¥1,000,000 (Direct Cost: ¥1,000,000)
Fiscal Year 1993: ¥1,100,000 (Direct Cost: ¥1,100,000)
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| Keywords | fulminant hepatic failure / IL-1beta / TNF-alpha / IL-6 / IL-1 receptor antagonist / regeneration / prognosis |
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| Research Abstract |
Fulminant hepatic failure (FHF) is characterized by massive necroinflammation of the liver tissue and is associated with high mortality Serum concentrations of IL-1beta, tumor necrosis factor-alpha (TNF-alpha), IL-6 and IL-1 receptor antagonist (IL-1Ra) were measured in 30 patients with FHF and in 23 patients with acute hepatitis (AH) before start of treatment and in 23 healthy controls. Levels of all four molecules were increased significantly in FHF compared with AH,in which values were higher than in the healthy controls. High serum levels of IL-1beta and a significantly reduced ratio of IL-1Ra to IL-1beta (IL-1Ra/ IL-1beta) were observed in FHF patients who subsequently died compared with subjects who survived. TNF-alpha and IL-6 concentrations were correlated with levels of human hepatocyte growth factor (hHGF), an index of hepatocyte regeneration. Although serum cytokine levels varied considerably between patients within each group studied, it is suggested that the striking elevation in proinflammatory cytokine levels in FHF may reflect both the insufficiency of hepatitis virus elimination and a failure to control a vicious cytokine cascade leading to overwhelming hepatocyte destruction rather than regeneration. The high cytokine levels observed in these patients and the significantly elevated IL-1Ra/IL-1beta ratio in FHF patients who survived compared with those who did not suggest the possible therapeutic use of cytokine antagonists for the control of this life-threatening disease.
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